Insecticidal isovaleric acid esters

ABSTRACT

Isovaleric acid ester derivatives and the optical isomers thereof expressed by the general formula I: ##STR1## wherein, R 1  represents hydrogen, methyl group or chlorine atom, and 
     R 2  represents hydrogen or cyano group.

This application is related to Japanese Patent Application Numbers Sho50-147601, Sho 51-144992, Sho 51-149079, Sho 52-20733, Sho 52-33479 andSho 52-37828.

DETAILED EXPLANATION OF THE INVENTION

The present invention relates to novel isovaleric acid ester derivativesand the optical and geometrical isomers thereof, a process for producingsaid derivatives and insecticides containing as active ingredient saidderivatives of the general formula I: ##STR2## wherein, R₁ represents,hydrogen, methyl group or chlorine atom, and

R₂ represents hydrogen or a cyano group.

Various alcohol components of cyclopropane carboxylic acid esters havebeen investigated and the esters are practically used. However, thecompounds are easily decomposed by light and therefore the outdoor useof these compounds is restricted.

As the result of recent investigations on acid components of the esters,more stable compounds to light than the conventional pyrethroids havebeen produced by substituting methyl group into halogen atom. However,taking the environmental pollution and chronic toxicity intoconsideration, insecticides having similar structure as those of naturalorganic compounds consisting of carbon, hydrogen, oxygen and nitrogenwill be advantageously used in the future. The present inventors haveintensively investigated on insecticides and found that the compound ofthe general formula (I) showed remarkably strong insecticidal actionagainst various sanitary and agricultural pests, while it is more stableto light than the conventional pyrethroids and is very low toxic againstwarm blooded animals.

Thus, the present invention is accomplished based on the knowledgementioned above. The compound of the formula (I) used as activeingredient in the present invention can be produced according to theordinary processes for producing esters by reacting a carboxylic acid ora reactive derivative thereof having the general formula IV: ##STR3##wherein, R₁ represents, hydrogen, methyl group or chlorine atom, with analcohol or a reactive derivative thereof having the formula V: ##STR4##wherein R₂ represents hydrogen or a cyano group.

Reactive derivatives of carboxylic acid are, for example, acid halides,acid anhydrides, lower alkyl esters and alkali metal salts. Reactivederivative of alcohol is, for example, chloride. The reaction is carriedout in a suitable solvent in the presence of organic or inorganic base,or acid as deacidificating agent or catalyst, if desired, and atelevated temperature at need. Representative compounds of the formula(I) are as follows: ##STR5##

The compounds of the present invention which are novel one are solid orliquid at room temperature and usually easily soluble in organicsolvent. Accordingly, they may be used as ingredients in insecticidalsprays in the form of emulsion, solution, powder, wettable powder andaerosol etc. In addition, they may be used as insecticides forfumigation by mixing them with some appropriate substrate such aspowdered wood and making mosquito incense sticks. Furthermore, thesecompounds show also strong effect as mosquito incense sticks when theyare employed as insecticides for heating and evaporating use. Namely,they are dissolved in a suitable organic solvent and the solution isabsorbed into a carrier and then the resulting product is heated on anappropriate heater. As the compounds of the present invention are morestable to light than the conventional pyrethroids, they may be used asagricultural insecticides.

Addition of some synergists into the compounds, for example,N-octylbicycloheptene dicarboxyimide (MGk-264 is the commercial name), amixture composed of N-octylbicycloheptene dicarboxyimide andalkylarylsulfonic acid salt (MGK-5026 is the commercial name),octachlorodipropylether, or pyperonylbutoxide, can enhance theinsecticidal effect.

The stability of this compound can be increased by adding some phenolic-or amine-antioxidants such as 2,6-di-tert-butyl-4-methylphenol (BHT),2,6-di-tert-butylphenol and the like. More highly active insecticidescan be obtained by joint use of the compounds with the conventionalpyrethroids such as allethrin, phthalthrin, resmethrin and furamethrin.

In the following, test results on the insecticidal effect of thecompounds used as active ingredients are given.

TEST EXAMPLE 1

Insecticidal effect by spraying test

With respect to each 0.2% white kerosene solution of 6 compounds of thepresent invention which are exemplified above (A), a white kerosenesolution containing 0.2% of each compound of the present invention and0.8% of pyperonylbutoxide (B), a white kerosene solution containing 0.1%of each compound of the present invention and 0.1% of phthalthrin (C), a0.2% white kerosene solution of allethrin and a 0.2% white kerosenesolution of phthalthrin, the relative effect values were estimated fromthe knockdown rate of house flies by spraying and the mortality after 24hours was obtained as follows:

    ______________________________________                                        Test                                                                          preparation (A)        (B)        (C)                                         ______________________________________                                        Allethrin   1.00  (26) --         --                                          Phthalthrin 2.15  (34) --         --                                          (1)         1.23  (84) 1.67 (100) 1.59  (90)                                  (2)         2.02 (100) 2.15 (100) 2.38 (100)                                  (3)         2.15 (100) 2.19 (100) 2.27 (100)                                  (4)         1.77 (100) 2.24 (100) 2.02 (100)                                  (5)         1.98 (100) 2.30 (100) 2.14 (100)                                  (6)         2.03 (100) 2.36 (100) 2.28 (100)                                  ______________________________________                                         The parenthesized values show the mortality after 24 hrs.                

TEST EXAMPLE 2

Insecticidal effect by fumigation test

Mosquito incense sticks containing each 0.5% active ingredient wereprepared and tested for the knockdown rate of red house mosquitoes.These tests were carried out in accordance with the procedure describedby Nagasawa, Katsuda and others in "Bochu-Kagaku" Vol. 16, page 176(1951). The test numbers of the active ingredients are the same as thoseof Example 1. The relative effect values of these mosquito incensesticks are as follows:

    ______________________________________                                        Test                                                                          preparation Probit 4   Probit 5   Probit 6                                    ______________________________________                                        Allethrin   1.00       1.00       1.00                                        (1)         1.30       1.35       1.40                                        (2)         1.34       1.37       1.39                                        (3)         1.62       1.65       1.70                                        (4)         1.46       1.49       1.52                                        (5)         1.58       1.61       1.64                                        (6)         1.61       1.65       1.69                                        ______________________________________                                    

The compounds according to the present invention are exemplified in thefollowing. The name of the compound is the same as mentioned in theexamples of active ingredient shown above.

EXAMPLE 1

A solution of 5.0 g of α-(4-chloroanilino)isovaleryl chloride in 15 mlof dry benzene was mixed with a solution of 4.7 g of3-phenoxy-α-cyanobenzylalcohol in 20 ml of dry benzene. When 3 ml of drypyridine were added into the solution as promotor of the condensation,crystals of pyridine hydrochloride were precipitated. The mixture wasallowed to stand in a tightly stopped vessel for one night and thepyridine hydrochloride was filtered off. The filtrate was dried oversodium sulfate and benzene was distilled off under reduced pressure toyield 7.5 g of 3'-phenoxy-α'-cyanobenzylα-(4-chloroanilino)-isovalerate.

EXAMPLE 2

2.0 g of α-anilinoisovaleric acid and 1.9 g of 3-phenoxybenzyl alcoholwere dissolved in 150 ml of benzene and 5 ml of concentratedhydrochloric acid were added into the solution with vigorously stirring.The mixture was refluxed with stirring and water distilled by azeotropywas removed with dehydrating agent. The reaction was continued for about4 hrs. with supplying benzene at need.

Then the reaction mixture was washed with an aqueous solution of sodiumhydrogencarbonate and with an aqueous solution of sodium chloride.Benzene was distilled off under reduced pressure to yield 3.1 g of3'-phenoxybenzyl α-anilinoisovalerate.

EXAMPLE 3

4.5 g of sodium α-(4-chloroanilino)-isovalerate and 4.5 g of3-phenoxybenzylchloride were dissolved in 50 ml of benzene and themixture was heated under reflux in nitrogen atmosphere for 3 hrs.

The reaction mixture was cooled and crystals of sodium chlorideprecipitated were filtered off. The filtrate was thoroughly washed withaqueous solution of sodium chloride and dried over sodium sulfate.Benzene was distilled off under reduced pressure to give 6.8 g of3'-phenoxybenzyl α-(4-chloroanilino)-isovalerate.

EXAMPLE 4

A mixture of 4.4 g of methyl α-(4-methylanilino)-isovalerate and 4.4 gof 3-phenoxy-α-cyanobenzyl alcohol was heated at 150° C. When thetemperature of the mixture reached to 150° C., 0.25 g of sodium wasadded to start distillation of methanol. Further 0.25 g of sodium wasadded into the mixture when distillation of methanol ceased whilekeeping the temperature of 150° C. The procedure mentioned above wasrepeated until theoretical amount of methanol was distilled off. Then,the reaction mixture was cooled and dissolved in ether. The etherealsolution was washed with diluted hydrochloric acid, aqueous solution ofsodium hydrogencarbonate and aqueous solution of sodium chloride anddried over sodium sulfate. Ether was distilled off under reducedpressure to yield 7.7 g of 3'-phenoxy-α'-cyanobenzylα-(4-methylanilino)-isovalerate.

EXAMPLE 5

7.4 g of α-anilino-isovaleric anhydride and 4.6 g of3-phenoxy-α-cyanobenzyl alcohol were mixed and 8 g of 98% sulfuric acidwas gradually added into the mixture. After conducting the reaction at80°-100° C. for 3 hrs, the reaction mixture was dissolved in ether. Theethereal solution was thoroughly washed with aqueous solution of sodiumhydrogen carbonate and then with aqueous solution of sodium chloride anddried over sodium sulfate. Ether was removed under reduced pressure toyield 7.3 g of 3'-phenoxy-α'-cyanobenzyl α-anilino-isovalerate.

EXAMPLE 6

Into a solution of 3.9 g α-(4-methylanilino)-isovaleric acid in 50 ml ofdimethylformamide were added 5.4 g of 3-phenoxybenzylbromide. 4 ml oftriethylamine were added into the mixture with stirring and the reactionwas carried out at 60°-80° C. for 3 hrs. The reaction mixture wasdissolved into ether and the ethereal solution was thoroughly washedwith aqueous solution of sodium hydrogen carbonate and then with aqueoussolution of sodium chloride. After drying the solution over sodiumsulfate, ether was removed under reduced pressure to yield 7.2 g of3'-phenoxybenzyl α-(4-methylanilino)-isovalerate.

REFERENCE EXAMPLE 1

Each 0.2 parts of Compounds (1), (2), (3) and (5) of the presentinvention is dissolved in sufficient white kerosene to form 100 parts of0.2% solution.

REFERENCE EXAMPLE 2

Each 0.2 parts of Compounds (2), (5) and (6) of the present inventionand 0.8 parts of pyperonylbutoxide are dissolved in sufficient whitekerosene to form 100 parts of solution.

REFERENCE EXAMPLE 3

Each 20 parts of Compounds (1), (2), (5) and (6) of the presentinvention, 10 parts of Solpol SM-200 (Tradename of Toho Chemical Co.)and 70 parts of xylene were mixed with stirring to form 20% emulsion.

REFERENCE EXAMPLE 4

Each 0.4 parts of Compounds (1), (4) and (6) of the present invention,0.1 part of resmethrin and 1.5 parts of octachlorodipropyl ether aredissolved in 28 parts of rectified kerosene. The solution is charged inan aerosol vessel and a jet-valve is attached to the vessel, throughwhich 70 parts of propellant (liquidized natural gas) are compressedinto the vessel to obtain an aerosol preparation.

REFERENCE EXAMPLE 5

Each 0.5 g of Compounds (1), (3) and (4) of the present invention and0.5 g of BHT are uniformly mixed with 99.0 g of substrate for mosquitoincense sticks such as pyrethrum extract powder, powdered wood andstarch etc. The resulting substance is molded into mosquito incensestick by a publicly known process.

REFERENCE EXAMPLE 6

Each 0.4 g of Compounds (1), (3) and (6) of the present invention and1.0 g of MGK-5026 are uniformly blended with 98.6 g of substrate formosquito incense stick. The resulting substance is molded into mosquitoincense stick by a publicly known process.

REFERENCE EXAMPLE 7

Each 3 parts of Compounds (2), (5) and (6) of the present invention and97 parts of clay are blended and pulverized to obtain 3% powder.

REFERENCE EXAMPLE 8

Each 40 parts of Compounds (2), (3), (5) and (6) of the presentinvention, 35 parts of diatomaceous earth, 20 parts of clay, 3 parts oflaurylsulfonic acid salt and 2 parts of carboxymethylcellulose arecrushed and blended to form wettable powder.

REFERENCE EXAMPLE 9

Each 20 parts of Compounds (2), (3), (4), (5) and (6) of the presentinvention, 20 parts of pyperonyl butoxide, 10 parts of solpol SM-200(Tradename of Toho Chemical Co.; emulsifier) and 50 parts of xylene weremixed with stirring to form 20% emulsion.

TEST EXAMPLE 3

Each 10 larvae at the third stage of tobacco cutworm (Prodenia lituraFabricius) were placed in a tall glass vessel and 1 ml portion of 1/200diluted solution of emulsion each containing Compounds (1), (2), (3),(4), (5) and (6) of the present invention and prepared by the sameprocedure as in Reference Example 3 was sprayed on the larvae. Then thelarvae were transferred into another glass vessel in which feed werepreviously placed. After 2 days, more than 80% of the larvae of tobaccocutworm in each case were killed.

TEST EXAMPLE 4

Each emulsion containing Compounds (1), (2), (3), (4), (5) and (6) ofthe present invention, which was prepared by the method mentioned inReference Example 3, was diluted with water to prepare 1/200 solution.100 l/tan (0.245 acre) of the solution was sprayed onto Japanese radishleaves at the 5-6 leaf stage, on which a lot of green peach aphid (Myzuspersicae Sulzer) was grown all over the surface. After 2 days, the greenpeach aphides decrease to less than 1/10 in each case when compared tothose before spraying.

TEST EXAMPLE 5

In a Wagner pot of 1/50,000 were planted rice-plants which grew for 45days after seeding. Each wettable powder containing Compounds (1), (2),(3), (4), (5) and (6) of the present invention, which was prepared bythe method mentioned in Reference Example 8 was diluted with water toprepare 1/400 solution. Each 10 ml/pot of the solution was sprayed ontothe rice plants. Each 20 adult smaller brown planthoppers (Laodelphaxstriatellus Fallen) were put into the pot which was covered with acylindrical metal net. After 1 day, more than 80% of the smaller brownplanthopper were killed in each case.

TEST EXAMPLE 6

Cotton plants which have grown in a seed-plot were sprayed with each 20ml of aqueous emulsion containing Compounds (1)-(6) of the presentinvention which was obtained by the method of Reference Example 9 insuch amount that the active ingredient was 2 mg per one plant (about 0.2kg/ha). On the second day and the fifth day after spraying, each 12leaves were taken from the cotton plants from which a piece of leaf of3.7 cm diameter was cut out. In a glass vessel of 9 cm diameter wereplaced a sheet of wet filter paper on which 4 leaves prepared above wereput in and 5 boll weevils were settled.

Mortality of each compound tested after 72 hrs is listed as follows:

    ______________________________________                                                        Day after spraying                                            Preparation     2 days      5 days                                            ______________________________________                                        Methylparathion  13 (%)      20 (%)                                           (1)             90          75                                                (2)             95          80                                                (3)             95          80                                                (4)             95          90                                                (5)             100         100                                               (6)             100         95                                                ______________________________________                                    

TEST EXAMPLE 7

Each wettable powder containing Compounds (2), (3), (5) and (6) of thepresent invention, which was prepared by the method mentioned inReference Example 8, was diluted with water to prepare 1/2000 solution.Cabbage leaves were thoroughly sprayed with the diluted solutionobtained above. After the coating was dried, the leaves were placed in apolyethylene plastic vessel with sand and 10 cabbage army worms(Mamestra brassicae Linne) were settled on the cabbage leaves.

After 2 days, more than 80% of the worms were killed in each case.

TEST EXAMPLE 8

One day before applying insecticide, about 200 aphides (Aphis craccivoraKoch) were put on each broad bean plant (Vicia faba L) in a pot. Eachemulsion containing Compounds (1), (2), (5) and (6) of the presentinvention, which has been prepared by the method of Reference Example 9was diluted with water to prepare 1/4000 solution. Each 10 ml/pot of thediluted solution was sprayed on the bean leaves which have swarmed withaphides by means of compressed air spray. After two days, any increaseof damage was not observed in each case.

TEST EXAMPLE 9

Each Emulsion containing Compounds (1), (2), (4), (5) and (6) of thepresent invention, which was prepared by the method in Reference Example3 and Reference Example 9 was diluted with water to prepare 1/2000solution. Cabbage leaves were immersed in the solution for about fiveseconds. After the coating is dried, the leaves were put in a glassvessel in which 10 larvae of cabbage army worm were settled. The larvaewere supplied twice at the date when the test leaves were prepared and 5days after that date. Mortality of Compounds tested after 24 hrs islisted as follows:

    ______________________________________                                               Reference Example 3                                                                          Reference Example 9                                     Preparation                                                                            first day  5th day   first day                                                                             5th day                                 ______________________________________                                        Salithion                                                                                40 (%)     5 (%)     45 (%)                                                                                5 (%)                                 (1)      70         60        90      85                                      (2)      75         60        95      85                                      (4)      85         65        95      85                                      (5)      85         75        100     95                                      (6)      85         65        100     90                                      ______________________________________                                    

From the above results, it is clear that the samples mixed withpyperonylbutoxide have the better effect at the first day and the fivedays later and the use of synergists enhances the effect of theCompounds of the present invention.

What is claimed is:
 1. Isovaleric acid ester derivatives and the opticalisomers thereof expressed by the general formula I: ##STR6## wherein, R₁represents hydrogen, methyl group or chlorine atom, andR₂ representshydrogen or cyano group.
 2. Isovaleric acid ester derivatives and thesteric isomers thereof according to claim 1, which are expressed by thegeneral formula II: ##STR7## wherein R₁ represents the same meaninggiven in claim
 1. 3. Isovaleric acid ester derivatives and the stericisomers thereof according to claim 1, which are expressed by generalformula III: ##STR8## wherein R₁ represents the same meaning given inclaim
 1. 4. Compound according to claim 2 having the formula: ##STR9##5. Compound according to claim 2 having the formula: ##STR10## 6.Compound according to claim 2 having the formula: ##STR11##
 7. Compoundaccording to claim 3 having the formula: ##STR12##
 8. Compound accordingto claim 3 having the formula: ##STR13##
 9. Compound according to claim3 having the formula: ##STR14##
 10. Process for producing isovalericacid ester derivatives of the general formula I: ##STR15## wherein, R₁represents hydrogen, methyl group or chlorine atom andR₂ representshydrogen or cyano group which process is characterized by reacting acarboxylic acid or a reactive derivative thereof having the generalformula IV: ##STR16## wherein, R₁ represents the same meaning givenabove with an alcohol or a reactive derivative thereof having thegeneral formula V: ##STR17## wherein R₂ represents the same meaninggiven above.
 11. An insecticidal composition comprising a carrier and asits essential ingredient an insecticidally effective amount of anisovaleric acid ester derivative of the general formula: ##STR18##wherein, R₁ represents hydrogen, a methyl group, or a chlorine atomandR₂ represents hydrogen or a cyano group.
 12. An insecticidalcomposition according to claim 11 wherein R₂ is hydrogen.
 13. Aninsecticidal composition according to claim 11 wherein R₂ is a cyanogroup.
 14. An insecticidal composition according to claim 11 wherein R₁is a chlorine atom and R₂ is hydrogen.
 15. An insecticidal compositionaccording to claim 11 wherein R₁ is a methyl group and R₂ is hydrogen.16. An insecticidal composition according to claim 11 wherein R₁ is achlorine atom and R₂ is a cyano group.
 17. An insecticidal compositionaccording to claim 11 wherein R₁ is a methyl group and R₂ is a cyanogroup.
 18. An insecticidal composition according to claim 11 whichadditionally contains a synergist selected from the group consistingof(a) N-octylbicycloheptene dicarboxyimide, (b) a mixture ofN-octylbicycloheptene dicarboxyimide and an alkylarylsulfonic acid salt,(c) octachlorodipropylether, and (d) pyperonylbutoxide.
 19. Aninsecticidal composition according to claim 18 wherein R₁ is a chlorineatom and R₂ is a cyano group and the synergist is pyperonyl butoxide.20. An insecticidal composition according to claim 18 wherein R₁ is amethyl group, R₂ is a cyano group and the synergist is pyperonylbutoxide.
 21. The method of combatting insects which comprises treatingthe material to be protected with an insecticidally effective amount ofan insecticidal composition as set forth in claim 11.